Category: News

The eTMF Exchange Mechanism Team – a sub-group of the TMF Reference Model project – has been working on a standard¹ for the transfer of TMF data between different eTMF systems for around three years. The objective is to define a simple standard that could be used in a number of scenarios:

• Final export of eTMF content for archiving;
• Interim transfer of eTMF to a central eTMF or other document repository;
• Migration of eTMF during mergers/acquisions;
• Migration of eTMF for system upgrades or change;
• Final transfer of eTMF content from third party (e.g. CRO) to sponsor.

We are very pleased to announce that the draft standard is now ready for industry review (see schedule – click for larger image).
A technical team has already been established for the technical review of the standard. This comprises representatives from companies such as Veeva, TransPerfect, Phlexglobal, Montrium, MasterControl, Arisglobal, Wingspan/IQVIA, goBalto, OpenText and Navitas. This team will be focussed on reviewing the metadata structure, XML definitions and structure, and adaptability and utility from a technical perspective.
The Exchange Mechanism team are now looking for volunteers to participate in a business review of the standard, looking at how well the specification as a whole would satisfy business needs. Volunteers will be invited to a one hour orientation meeting in December to get insights on the review and feedback process. The estimated total effort for the meeting, your review and submission of feedback is four to six hours over a 6 – 8 week period.
To join the team and become a business reviewer, simply register online and select “Exchange Mechanism” from the list of active work groups. You must have the time available to participate; there will be other opportunities for you to have visibility of the draft specification if this is your only reason for joining!
————
¹Standard: the term is used here in its general sense i.e. “used or accepted as normal or average; viewed as authoritative and so widely read”. Currently, the specification will not be authorized or published by a recognized standards body, though this may be considered at a future time. Following the closure of the OASIS eTMF Technical Committee prior to finalization of an eTMF standard, this is the only eTMF technical standard under development at this time and has the support of all major eTMF vendors.

The TMF Reference Model has been developed to be equally applicable to clinical trials using investigational medicinal product (IMP) and those using medical devices and diagnostics (MD&D). The model includes metadata to designate certain artifacts as corresponding to IMP trials or to device trials. However, in practice, it is sometimes difficult to apply the model to MD&D trials. The terminology used for artifacts or the language used to describe the definition and purpose of an artifact is often too heavily slanted towards IMP trials. For example, zone 6 for MD&D trials should correspond to the test device or test diagnostic article but this is not self-evident in the way the model is worded.
It is for these reasons that we have initiated a new sub-team within the TMF Reference Model Project to identify how the model might be improved for use on MD&D trials. This might include, for example, enhancing the definition and purpose for existing artifacts so that the text is more meaningful for those trials. It might include the additional of sub-artifacts that are specific to MD&D trials. It might even include the additional of new artifacts!
If you have experience of MD&D trials and would like to participate in this activity, please apply NOW to join the group…. or encourage a knowledgeable colleague to join! It is hoped that this will be a fairly short-term project with deliverables expected in Q1 2018. Please only apply to join if you can spare the time to contribute; the output will be freely available to everyone. To join, please send a request to  devices+subscribe@tmfrefmodel.groups.io, stating who you are and your company.

We are pleased to announce the publication of the final deliverables from the Milestones Sub-group, led by Kathleen Kirby.
The purpose of this document is to define the latest point in time when an artifact is to be submitted / filed within the TMF. Of course, there is a regulatory expectation that artifacts are filed contemporaneously so our guide simply identifies the latest filing time that we think is reasonable. In addition, as this is a guide, each Sponsor should modify the Milestone/Event list according to their practices. The intention of Milestones/Events is to ensure maintenance of the TMF on an ongoing basis.
Many artifacts will require updating throughout the trial. We have assigned the first Milestone/Event where the artifact would typically first appear in the TMF. At the time Milestones/Events were incorporated into the TMF Reference Model, only one Milestone/Event was assigned to each artifact for each level. Future plans include adding in additional Milestones/Events at each level.
It should be noted that if the Sponsor wants FEWER Study Milestones / Events to track to (for example, to align with a Clinical Trial Management System), they can roll up into a later Study Milestone / Event as these are listed broadly in chronological sequence. Conversely, if the Sponsors wants MORE Study Milestones / Events to track to, they can create their own OR utilize the sub activities identified.
If artifacts are filed and then updated, the updated artifacts are to be filed contemporaneously with collection (in real time).
For further information, including a short list of Frequently Asked Questions and a copy of the TMF Reference Model that includes the milestones and events (see Excel columns U-Z), please refer to the Resources web page.

It has been over eight years since the charter for the TMF Reference Model was published (April 2009). A lot has changed in those eight years but the charter has remained the same. So the Steering Committee felt it was high time for a review!
The Steering Committee are pleased to announce the publication of a revised version of the charter. This revision includes much content that is largely the same as the original version, though structured a little differently to make the text flow more logically. However, the new charter also includes some changes to recognise where the project is today:

• includes governance of the project by a Steering Committee;
• includes the requirement for Steering Committee members to also be DIA members (the project is a working group within the DIA Document & Records Management Community);
• recognises the valuable contribution made by non-DIA members;
• includes the maintenance of member information (to comply with data protection regulations);
• includes the maintenance of this website: and
• clarifies the scope of the project.

On the final point – project scope – the Steering Committee recognised that from time to time the project team had got involved in several issues that, whilst being important and related to TMF management, they were not directly related to the development or implementation of the TMF Reference Model. The new charter clarifies the limited scope of the project and will work with the DIA Document & Records Management Community to progress activities that are out of scope.
The new document can be found on our Resources web page.

Successful management of a TMF, whether in paper or electronic form, is highly dependent on the classification system (e.g. TMF Reference Model) and the ability for a reviewer to identify and locate documents by specific attributes, such as the document date. However, deciding which date to use as the “document date” can often be subjective and therefore creates inconsistency in file maintenance; or even worse, documents can be perceived as being missing because a document is misfiled or mis-classified due to an arbitrary selection of the document date.
The TMF Reference Model Project’s Date Conventions workgroup was formed to solve this problem. It is comprised of individuals who represent a wide variety of perspectives, enabling the resource to be adaptable to all users and environments. The group consists of representation from:

• Large and small organisations
• Pharma, CROs, eTMF vendors and non-profit
• Paper TMF, eTMF and hybrid environments
• Numerous functional roles, from the daily operational end-user to the TMF Specialist

This workgroup is excited to announce the release of two new resources which bring together these decades of experience, in order to improve consistency in TMF management:

• Suggested date conventions added to the TMF Reference Model for each artifact (see column AD)
• A supplemental guidance document that provides:
  • Rationale for creating date conventions
  • Definitions for common terms
  • Standard rules by document type and for ambiguous dates (e.g. month and year, but no day) and date format
  • How to implement date conventions within your organisation

These two resources are now available to download on our Resources web page.

What is Quality Control and what does it look like for your clinical trial? Those are some of the questions you may have about TMF Quality that are addressed by The Trial Master File Reference Model Quality Group’s (TMF RM QG) latest output documents. They have recently released their expert recommendations for a thorough and complete TMF review. The group, with representation from across the world, released straightforward guidelines to improve your TMF quality.
The review of the TMF is two-part process that consists of quality control of both the individual TMF documents as well as the entire TMF. The group recommends ensuring each document meets the criteria of the mnemonic “R.U.T.O.L.A.” to be considered “TMF Ready.” The RUTOLA criteria will definitely get you out of the rut of the old guessing game when it comes to QC of TMF documents! Each document should be:

• Retrievable – A document that gets filed should be quickly and efficiently accessible utilizing appropriate metadata and an organized filing system, such as the TMF Reference Model.
• Unique – Each required document is present without duplicates.
• Translations – All required translation documentation is present.
• Original – Documents are unaltered.
• Legible – All document information is comprehensible and clean with identifiable stamps and signatures
• Applicable – The document is necessary to support the story of a clinical trial and is required as per the filing system (TMF Reference Model) or the company’s policy.

TMF Quality Tools
Almost every undertaking requires the right tools and ensuring TMF quality is no different. The TMF RM QG also outlines some essential tools to pave your way to TMF quality success. These tools include TMF Reference Model (ideally customised to fit the needs of the specific study), a comprehensive TMF Management Plan, and a Corrective Action Plan.
This is a small extract of the work that the TMF RM QG have published. You can download the full document, as well as a PowerPoint presentation slide deck that was presented to the TMF Reference Model group in November 2016 from our Resources web page.

Many of you will be aware that, as a deliverable of the TMF Reference Model initiative, the TMF Survey is designed to provide insights from sponsors, CROs, inspectors, trial sites and other stakeholders, for both paper and electronic TMF management. This is the only non-commercial TMF survey conducted by and for the TMF stakeholder community.
The intent of the survey remains true to the Reference Model key objectives:
• to identify TMF trends;
• to assess  changes in industry directions;
• to measure the impact of TMF practices.
It’s been a little while since the last survey was released and you’ll notice some new questions this year. We’re keen to understand who our Sponsor contributors are; for example, do Sponsors from Diagnostics or Device organisations now have an increased representation in the TMF Reference Model initiative? We would also like to understand more regarding Inspection experiences and specifically Inspector Access.
As usual, the results of the survey will be available for all contributors, so if you‘d like a copy, please provide your email address at the end of the survey. We welcome participation from sponsors, CROs, inspectors, trial sites and other stakeholders who are involved in clinical trial activities.
Click HERE to go to the survey. Thank you in advance for your participation!

The adoption of v3.0 of the TMF Reference Model across industry has been phenomenal. Data suggests that the Reference Model is being used by the majority of commercial clinical trial sponsors and contract research organisations. But we know that the Model is not perfect and it is only when you start to implement it within an organisation that deficiencies become apparent….. despite our very best efforts to get it right first time!
So we really need to hear from you and incorporate improvements into future versions of the Model. The Steering Committee have recently agreed in principle a new version control process (to be published shortly) whereby we can make small maintenance releases of the Model that have no required impact on existing implementations of the Model but help with understanding and adoption. This will make it easier for us to introduce improvements without having to wait for a major release.
How can you help? We have a simple feedback form on our website to collect three types of comments:
Proposal for a new artifact
If you think the model is completely missing an artifact, let us know. Remember that artifacts do not always correspond to a single document but are best considered as “folders” to file a range of document types that meet a specified regulatory purpose. So please read the definition/purpose in the Model before proposing something new. Additional artifacts have a significant impact to those who have already adopted the Model so we need to be sure your suggestion cannot be met by modifying an existing artifact. If you are proposing the addition of multiple artifacts, please complete a new form for each proposed artifact.
Change existing artifact
Select this option if you think that information in the Model that is associated with an existing artifact needs to be changed. For example, you may think the artifact should be in a different zone. Or you think an artifact is associated with the wrong filing level, or needs the definition/purpose revising. If you are proposing changes to multiple artifacts, please complete a new form for each affected artifact.
General comment
Please only use this option if you have a more general comment to make regarding the Model, for example a comment regarding a whole zone. Be as clear as you can and provide a rationale for why you are making the comment.
As the Reference Model is maintained by industry volunteers, we are unable to respond to individual posted comments or to enter into discussions regarding the acceptability of your comments. We may however get in touch with you if we need further clarification and we will review every comment that we receive.

An inspection has been announced and you want to prepare the TMF for the inspection. What do you need to think of and what activities are typically conducted to prepare for the inspection?
These and many other questions have been addressed through the work that has been performed by the ‘Inspection Readiness’ TMF Reference Model subgroup. The scope of the work was to develop a toolkit of inspection preparation checklists, lessons learned and other resources that are available in the public domain. In particular, the subgroup discussed activities that organisations typically undertake to prepare for inspections and the roles performing those activities. The subgroup looked into different options to consolidate this and make it usable for other organisations.
The outcome is that the subgroup has gathered best practices for preparation of the TMF for inspection and these activities are listed in the Inspection Readiness RACI. The toolkit can be downloaded free of charge from our Resources web page.
The Inspection Readiness RACI can be used both for paper TMF, eTMF and hybrid TMFs. It can be adapted with the roles specific to the organisation using it and will help structure the inspection preparations and give a clear overview of activities, roles and responsibilities.

The TMF Reference Model was last updated in June 2015 so you may be thinking that all has gone quiet and nothing is happening. You couldn’t be farther from the truth! We currently have TWELVE sub-groups working on various initiatives concerning TMF management, involving around 90 members of the TMF Reference Model project team. These teams are all meeting as need to push forward their project. The ‘TMF Quality Control‘ group have completed their work and recently presented their draft output to the Steering Committee. The ‘Milestones’ group also presented their interim work to the Steering Committee to check they were aligned with the set objectives.
You can find details of all of the current work groups in our Roadmap but here’s the complete list:

• eTMF Interoperability (eTMF Exchange Mechanism)
• Reference Model Implementation Toolkit
• Annual TMF Survey
• Reference Model Upgrade User Guide
• Metadata
• Recommended Dating Conventions
• Single-site Reference Model Template
• Artifact Sub-types
• Inspection Preparation
• Milestones
• Country-Specific Artifacts
• TMF Quality Control

Some of these groups are nearing completion of their objectives but if you have an interest in getting involved, please contact us and we’ll put you in touch with the team lead. You need to be a member of the TMF Reference Model project team to join a team.